Finding functions of phase separation in the presynapse

Abstract

Synapses are the basic units of neuronal communication. Understanding how synapses assemble and function is therefore essential to understanding nervous systems. Decades of study have identified many molecular components and functional mechanisms of synapses. Recently, an additional level of synaptic protein organization has been identified: phase separation. In the presynapse, components of the central active zone and a synaptic vesicle-clustering factor have been shown to form liquid-liquid phase-separated condensates or hydrogels. New in vivo functional studies have directly tested how phase separation impacts both synapse formation and function. Here, we review this emerging evidence for in vivo functional roles of phase separation at the presynapse and discuss future functional studies necessary to understand its complexity.